Selenium is an essential trace element and is the functional component of several important enzymes and which is increasingly also recognized for its anticarcinogenic properties. The glutathione peroxidases, for example, prevent the build-up of hydrogen peroxide and lipid hydroperoxides and thus help to protect cells and tissues from damage by reactive oxygen species. Since oxygen radicals attacking DNA may cause mutations resulting in the transformation of normal cells into cancer cells, selenium by virtue of its antioxidant properties can counteract these processes thereby acting as a cancer-protecting agent.
Selenium in addition to its anti-mutagenic properties may alter carcinogen metabolism and prevent DNA methylation and other mechanisms believed to play a role in carcinogenesis. Selenium is also required for the maintenance of the functions of the immune system. At pharmacological levels, selenium is known to exert cytotoxic effects on tumor cells without adversely affecting normal cells. For example, sodium selenite added to the growth media caused the selective destruction of human hepatoma and lung cancer cells without affecting normal embryonic liver or lung cells; see: S. Y. Yu, et al, Biol. Trace El. Res. 15: 243-255 (1987); A. Pung et al., Biol. Trace El. Res. 14: 29-42 (1987). Selenium compounds accordingly are receiving attention as potential cancer therapeutic agents. Selenium preparations for a variety of therapeutic uses are already available, most of which are for oral administration or by injection.
A number of selenium-containing preparations for topical applications have also been claimed. For example, in U.S. Pat. No. 4,865,840, the use of lotions or creams containing selenomethionine was claimed for the prevention of ultraviolet radiation-induced skin damage. In U.S. Pat. No. 4,512,977, selenium compounds are claimed for the topical treatment of damage caused by surgical incisions, lacerations and burns. The compounds claimed in these patents are water soluble.
A lipid soluble organo selenium compound, di-n-hexyl diselenide, has previously been used in cancer therapy, but only in preparations for oral or parenteral administration (E. Revici, Research in Physiopathology as Basis of Guided Chemotherapy, Van Nostrand Company, New York, 1961, pp.512-518). The related compound di-n-diheptyl diselenide, was shown to inhibit the growth of several human cancer cell lines in cell cultures [see G. Scambia et al., Anticancer Res. 9: 1697-1700, (1989). In German Patent 43 20694.8-41, preparations containing dialkyl diselenides were claimed for the topical treatment of warts. For cancer treatment, preparations containing dialkyl diselenides and related compounds have previously been claimed only for oral or parenteral administration. For example, in DE-3408362 C2, dialkyl diselenides of the general composition R—Se—Se—R, with R being an alkyl or alkenyl group with an odd number of carbon atoms in combination with an aliphatic ketone were claimed as oral and parenteral drugs for the treatment of cancer. In EP-0095663, the reaction product of selenium with eleostearic acid was claimed as an anti-neoplastic drug for oral or parenteral administration.